The antibiotic nogalamycin, and a process for its preparation, are described in U.S. Pat. No. 3,183,157. The structure of nogalamycin can be shown as follows: ##STR1##
Antibiotics nogalarol and nogalarene, produced by acid hydrolysis of nogalamycin, and O-methylnogalarol, produced by acidic methanolysis of nogalamycin or nogalarol, are disclosed in U.S. Pat. No. 3,501,569.
Nogalamycinic acid is prepared by chemical modification of nogalamycin as disclosed in U.S. Pat. No. 4,064,341. The structure of nogalamycinic acid is as follows: ##STR2##
Nogalamycinic acid can be converted to nogamycin by contacting it with dimethylformamide (see U.S. Pat. No. 4,064,340). Nogamycin has the following structural formula: ##STR3##
It is now found that the nogamycin prepared in the process of the above citation is dis-nogamycin. In dis-nogamycin and its analogs, the 9-hydroxy and 7-substituents are on opposite sides of the ring system.
U.S. Pat. No. 4,086,245 and U.S. application Ser. No. 924,975, now U.S. Pat. No. 4,183,860 concerns 7-O-alkylnogarols and their preparation from nogamycin.
Acid alcoholysis of nogamycins is the process used in the above preparations of 7-O-alkylnogarols having the following formulas: ##STR4## wherein R is an alkyl group of from 1 to 4 carbon atoms, inclusive.
Additional prior art includes disclosure by Tong et al.; in Abstracts of Papers, 175th ACS meeting. Medicinal Division, paper 48, for a process which treats daunomycinone with 2-aminoethanethiol in trifluoroacetic acid solution to obtain two diastereomers of a 7-(2-aminoethylthio) derivative.
Demonstrated advantageous biological use for the 7-O-alkylnogarols are included in U.S. Pat. No. 4,086,245 and copending U.S. Ser. No. 924,975. Nogamycin itself has a demonstrated advantageous use in U.S. Pat. No. 4,064,340.
Applicants pending U.S. application Ser. No. 060,326 filed July 25, 1979, now abandoned describes structurally novel nogamycin, 7-nogarols and 7-deoxynogarols having the formula: ##STR5## wherein B is a nucleophile from a group comprising nogalosyl, a sulfide anion, organic acid anion, amino, substituted amino and carbanion, with the proviso that B is not -O-lower alkyl and T is hydroxyl such that B and T are attached to the ring system of I in the con configuration. Con compounds are defined as those in which the 9-hydroxy and 7-B substituents are either both above or below the ring system.